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- Albertsson-Wikland, Kerstin, et al.
(author)
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Mortality Is Not Increased in Recombinant Human Growth Hormone-treated Patients When Adjusting for Birth Characteristics
- 2016
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In: Journal of Clinical Endocrinology and Metabolism. - : ENDOCRINE SOC. - 0021-972X .- 1945-7197. ; 101:5, s. 2149-2159
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Journal article (peer-reviewed)abstract
- Objective: This study aimed to investigate whether reported high mortality in childhood recombinant human GH (rhGH)-treated patients was related to birth-characteristics and/or rhGH treatment. Design and Setting: We sought to develop a mortality model of the Swedish general population born between 1973 and 2010, using continuous-hazard functions adjusting for birth characteristics, sex, age intervals, and calendar year to estimate standardized mortality ratio (SMR) and to apply this model to assess expected deaths in Swedish rhGH-treated patients with idiopathic isolated GH deficiency (IGHD), idiopathic short stature (155) or born small for gestational age (SGA). Participants:The general population: Swedish Medical Birth Register (1973-2010: 1 880 668 males; 1 781 131 females) and Cause of Death Register (1985-2010). Intervention Population: Three thousand eight hundred forty-seven patients starting rhGH treatment between 1985 and 2010 and followed in the National GH Register and/or in rhGH trials diagnosed with IGHD (n = 1890), ISS (n = 975), or SGA (n=982). Main Outcome Measures: Death. Results: Using conventional models adjusting for age, sex, and calendar-year, the SMR was 1.43 (95% confidence interval, 0.89-2.19), P = .14, observed/expected deaths 21/14.68. The rhGH population differed (P amp;lt; .001) from the general population regarding birth weight, birth length, and congenital malformations. Application of an Advanced Model: When applying the developed mortality model of the general population, the ratio of observed/expected deaths in rhGH-treated patients was 21/21.99; SMR = 0.955 (0.591-1.456)P = .95. Model Comparison: Expected number of deaths were 14.68 (14.35-14.96) using the conventional model, and 21.99 (21.24-22.81) using the advanced model, P amp;lt; .001, which had at all ages a higher gradient of risk per SD of the model, 24% (range, 18-42%; P amp;lt; .001). Conclusions: Compared with the general Swedish population, the ratio of observed/expected deaths (21/21.99) was not increased in childhood rhGH-treated IGHD, ISS, and SGA patients when applying an advanced sex-specific mortality model adjusting for birth characteristics.
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- Albertsson-Wikland, Kerstin, 1947, et al.
(author)
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Mortality is not increased in rhGH-treated patients when adjusting for birth characteristics.
- 2016
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In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 101:5, s. 2149-2159
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Journal article (peer-reviewed)abstract
- Objective: This study aimed to investigate whether reported high mortality in childhood recombinant human GH (rhGH)-treated patients was related to birth-characteristics and/or rhGH treatment. Design and Setting: We sought to develop a mortality model of the Swedish general population born between 1973 and 2010, using continuous-hazard functions adjusting for birth characteristics, sex, age intervals, and calendar year to estimate standardized mortality ratio (SMR) and to apply this model to assess expected deaths in Swedish rhGH-treated patients with idiopathic isolated GH deficiency (IGHD), idiopathic short stature (155) or born small for gestational age (SGA). Participants:The general population: Swedish Medical Birth Register (1973-2010: 1 880 668 males; 1 781 131 females) and Cause of Death Register (1985-2010). Intervention Population: Three thousand eight hundred forty-seven patients starting rhGH treatment between 1985 and 2010 and followed in the National GH Register and/or in rhGH trials diagnosed with IGHD (n = 1890), ISS (n = 975), or SGA (n=982). Main Outcome Measures: Death. Results: Using conventional models adjusting for age, sex, and calendar-year, the SMR was 1.43 (95% confidence interval, 0.89-2.19), P = .14, observed/expected deaths 21/14.68. The rhGH population differed (P < .001) from the general population regarding birth weight, birth length, and congenital malformations. Application of an Advanced Model: When applying the developed mortality model of the general population, the ratio of observed/expected deaths in rhGH-treated patients was 21/21.99; SMR = 0.955 (0.591-1.456)P = .95. Model Comparison: Expected number of deaths were 14.68 (14.35-14.96) using the conventional model, and 21.99 (21.24-22.81) using the advanced model, P < .001, which had at all ages a higher gradient of risk per SD of the model, 24% (range, 18-42%; P < .001). Conclusions: Compared with the general Swedish population, the ratio of observed/expected deaths (21/21.99) was not increased in childhood rhGH-treated IGHD, ISS, and SGA patients when applying an advanced sex-specific mortality model adjusting for birth characteristics.
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- Günther, Mattias, et al.
(author)
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Neuroprotective effects of N-acetylcysteine amide on experimental focal penetrating brain injury in rats
- 2014
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In: Neuroscience Meeting, Washington DC, 2014 Nov 15-21. ; , s. 486.06-
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Conference paper (other academic/artistic)abstract
- Background The beneficial effects of N-acetylcysteine (NAC) on CNS ischemia and after TBI in animal models are well documented. However, the bioavailability of NAC is very low. N-acetylcysteine Amide (NACA) is a newly modified form of N-acetylcysteine that contains an amide group in place of the carboxyl group of NAC. NACA has more efficient membrane permeation and crosses the blood brain barrier. We examined the effects of NACA in the secondary inflammatory response following focal penetrating TBI in rats. Material and methods Focal penetrating TBI were produced in a total of 24 male Sprague-Dawley rats randomly selected for treatment (n=5), non-treatment (n=5) and sham (n=4). The treated animals were given NACA 300 mg/kg ip after 5 min and in the 24h survival group a bolus of 300 mg/kg ip after 4h. After 2h and 24h the brains were removed, cut in 14 µm coronal sections and subjected to immunohistochemistry, immunofluorescence, Fluoro-Jade and TUNEL analyses. Results NACA treatment decreased neuronal degeneration by Fluoro-Jade at 24h (p
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- Johansson, Lovisa, et al.
(author)
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Genetic variance in the adiponutrin gene family and childhood obesity.
- 2009
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 4:4
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Journal article (peer-reviewed)abstract
- AIM: The adiponutrin gene family consists of five genes (PNPLA1-5) coding for proteins with both lipolytic and lipogenic properties. PNPLA3 has previously been associated with adult obesity. Here we investigated the possible association between genetic variants in these genes and childhood and adolescent obesity. METHODS/RESULTS: Polymorphisms in the five genes of the adiponutrin gene family were selected and genotyped using the Sequenom platform in a childhood and adolescent obesity case-control study. Six variants in PNPLA1 showed association with obesity (rs9380559, rs12212459, rs1467912, rs4713951, rs10947600, and rs12199580, p<0.05 after adjustment for age and gender). Three variants in PNPLA3 showed association with obesity before, but not after, adjustment for age and gender (rs139051, rs12483959, and rs2072907, p>0.05). When analyzing these SNPs in relation to phenotypes, two SNPs in the PNPLA3 gene showed association with insulin sensitivity (rs12483959: beta = -0.053, p = 0.016, and rs2072907: beta = -0.049, p = 0.024). No associations were seen for PNPLA2, PNPLA4, and PNPLA5. CONCLUSIONS: Genetic variation in the adiponutrin gene family does not seem to contribute strongly to obesity in children and adolescents. PNPLA1 exhibited a modest effect on obesity and PNPLA3 on insulin sensitivity. These data, however, require confirmation in other cohorts and ethnic groups.
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- Johansson, Lovisa, et al.
(author)
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Interaction between PPARG Pro12Ala and ADIPOQ G276T concerning cholesterol levels in childhood obesity.
- 2009
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In: International Journal of Pediatric Obesity. - : Informa UK Limited. - 1747-7174 .- 1747-7166. ; 4, s. 119-125
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Journal article (peer-reviewed)abstract
- Aim. The aim of this study was to investigate the role of two candidate gene polymorphisms for insulin resistance and lipid levels in obese children and adolescents. Methods. Two markers of insulin resistance and lipid levels, Pro12Ala in peroxisome proliferator-activated receptor-gamma2 (PPARG) and G276T in adiponectin (ADIPOQ), were genotyped in 285 obese children and adolescents. As the apolipoprotein E (APOE) polymorphisms C112R and R158C are known to have a profound impact on lipid levels in both children and adults, results were adjusted for APOE genotype. Results. We found no association for PPARG or ADIPOQ polymorphisms with Body Mass Index (BMI), High Density Lipoprotein (HDL)-cholesterol, triglycerides or Insulin Resistance estimated by Homeostasis Model of Assessment (HOMA-IR). Wild type carriers of PPARG Pro12Ala (p<0.05), homozygous carriers of the variant allele of ADIPOQ G276T (p<0.001) and epsilon4 carriers of APOE (p<0.001) had higher total and low density lipoprotein (LDL)-cholesterol levels adjusted for age, gender, BMI and insulin sensitivity. A PPARG/ADIPOQ risk genotype combination was identified by analysis of covariance (ANCOVA) comparing all existing combinations. Carriers of PPARG Pro/Pro and ADIPOQ 276 T/T had higher total (5.0 [4.1-5.8] vs. 4.1 [3.6-4.6]mmol/l) and LDL-cholesterol levels (3.7 [2.9-4.5] vs. 3.0 [2.5-3.5]mmol/l) compared with carriers of other combinations (p<0.001). Importantly, the PPARG and ADIPOQ associations were unaffected when adjusting for APOE genotype. Conclusions. Genetic variants in candidate genes for insulin resistance are associated with cholesterol levels in obese children and adolescents, and may offer additional information in the risk assessment of obese children.
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- Kamel, Ashraf F, et al.
(author)
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Age-dependent regulation of lipogenesis in human and rat adipocytes.
- 2004
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In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 89:9, s. 4601-4606
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Journal article (peer-reviewed)abstract
- The regulation of adipocyte metabolism is of importance for adipose tissue growth and therefore also for the development of obesity. This study was designed to investigate the regulation of basal and insulin-induced lipogenesis, glucose transport, and glucose transporter protein expression in human and rat adipocytes from different age groups. The study included 21 infants, 21 children, nine adults, and 80 male weaned and 20 male adult Fischer rats. The lipogenesis experiments were performed under conditions at which glucose transport is rate limiting. Basal lipogenesis was approximately three times higher in infants and children than in adults, whereas insulin-induced lipogenesis was two times higher in infants than in children and adults. In rats, basal lipogenesis, insulin-induced lipogenesis, and insulin sensitivity were two times higher in weaned than in adult animals. Moreover, basal and insulin-induced glucose transport were two times higher in weaned than in adult rats. No differences were detected in GLUT1 or GLUT4 content between any of the age groups in human or in rat adipocytes. In conclusion, basal and insulin-stimulated lipogenesis are increased in adipocytes early in life. This may promote adipose tissue growth in early age. The data indicate that age-dependent variation in basal and insulin-stimulated lipogenesis is differently regulated.
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- Rössner, Sophia M., et al.
(author)
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Alternative methods of insulin sensitivity assessment in obese children and adolescents
- 2008
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In: Diabetes Care. - Alexandria, Va. : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 31:4, s. 802-804
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Journal article (peer-reviewed)abstract
- OBJECTIVE—To validate fasting indexes against minimal model analysis (MMOD) of the frequently sampled intravenous glucose tolerance test (FSIVGTT) in an obese pediatric population.RESEARCH DESIGN AND METHODS—FSIVGTT-MMOD results were compared with homeostasis model assessment of insulin resistance (HOMA-IR) and fasting insulin with the sample stratified by sex, puberty, and sensitivity index (Si) median in 191 children (82 males and 109 females, 13.9 ± 2.9 years of age, BMI 36.9 ± 6.2 kg/m2, BMI SD score 6.1 ± 1.6).RESULTS—Across pubertal groups, correlation coefficients between Si and HOMA-IR ranged from −0.43 to −0.78 in males and from −0.53 to −0.57 in females (age and BMI adjusted, P < 0.05 in all instances). Similar results were seen for fasting insulin. In females, the relationship was significantly weaker in more-insulin-resistant subjects.CONCLUSIONS—The validity of fasting indexes in explaining Si was sex dependent, varied with pubertal stage, and in females was influenced by degree of insulin sensitivity. In obese pediatric populations, we generally discourage the use of fasting indexes, although the validity varies within subgroups.
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